Single-Site Template Nanoparticles for Monoclonal SBS Clustering
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Solution Overview
Problem
Current sequencing by synthesis (SBS) technologies face inefficiencies due to suboptimal use of substrate surface area for seeding and clustering of template polynucleotides, leading to increased time, cost, and complexity in data processing, particularly when clusters are not spatially distinct or polyclonal.
Innovation Solution
The use of nanoparticles with a single template site for bonding a template polynucleotide and multiple accessory sites for accessory oligonucleotides, promoting monoclonal clustering by ensuring each template polynucleotide is attached to a separate nanoparticle, thereby reducing polyclonal clusters and maximizing substrate surface utilization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If template polynucleotides are seeded densely on substrate surface to maximize surface area utilization, then sequencing throughput increases, but polyclonal clusters form reducing sequencing accuracy
Solution Approach 1:
The patent introduces nanoparticles as intermediary carriers that bind template polynucleotides before they are deposited on the substrate. Each nanoparticle acts as a separate seeding unit with a single template polynucleotide, ensuring that even at high densities, each cluster remains monoclonal. This intermediary approach allows dense seeding while maintaining sequencing accuracy by preventing template polynucleotide proximity issues.
2Area of stationary object
If multiple template polynucleotides seed close together on substrate, then substrate surface area is utilized efficiently, but spatially distinct clusters cannot be resolved
Solution Approach 1:
The patent segments the template polynucleotide binding function across multiple nanoparticle carriers rather than direct substrate binding. Each nanoparticle is spaced apart on the substrate, creating physically separated seeding sites. This segmentation ensures that even though nanoparticles are distributed densely to maximize surface area, the actual template polynucleotide clusters remain spatially distinct and resolvable by imaging systems.
3Quantity of substance
If conventional seeding methods are used to maximize template polynucleotide attachment, then sequencing information quantity increases, but data processing complexity increases
Solution Approach 1:
By using nanoparticles as intermediaries, the patent creates a one-to-one correspondence between nanoparticles and template polynucleotides, simplifying the relationship between physical features and sequence data. Each nanoparticle's position and identity can be tracked through the sequencing process, creating straightforward linkage between spatial coordinates and sequence information, thereby reducing data processing complexity while maintaining high sequencing information quantity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach enhances the efficiency of SBS by increasing the seeding density and monoclonality of clusters, reducing time and cost, and simplifying data analysis by ensuring clear separation of clusters, thus improving sequencing outcomes.
Implementation Method 1
a single template site for bonding a template polynucleotide to the scaffold selected from a covalent template bonding site and a noncovalent template bonding site
Implementation Method 2
a single template site for bonding a template polynucleotide to the scaffold selected from a covalent template bonding site and a noncovalent template bonding site
Implementation Method 3
a plurality of accessory sites for bonding accessory oligonucleotides to the scaffold selected from covalent accessory oligonucleotide bonding sites and noncovalent accessory oligonucleotide bonding sites
Implementation Method 4
a plurality of accessory sites for bonding accessory oligonucleotides to the scaffold selected from covalent accessory oligonucleotide bonding sites and noncovalent accessory oligonucleotide bonding sites
Data Source
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AI summary
Provided is a nanoparticle including a scaffold, a single template site for bonding a template polynucleotide to the scaffold, and a plurality of accessory sites for bonding accessory oligonucleotides to the scaffold, wherein the scaffold is selected from an asymmetrical acrylamide polymer one or a dendrimer including lysyl constitutional repeating units, the single template site for bonding a template polynucleotide to the scaffold is selected from a covalent template bonding site and a noncovalent template bonding site and the plurality of accessory sites for bonding accessory oligonucleotides to the scaffold are selected from covalent accessory oligonucleotide bonding sites and noncovalent accessory oligonucleotide bonding sites. Also provided are methods of using the nanoparticle.